The main objective of this new Program Project Grant, as well as the previous proposal is a collaborative effort to define the fundamental principles governing catecholamine gene expression and regulation. Project I, Regulation of catecholamine enzyme gene expression during neuronal degeneration and regeneration, studies the regulation of catecholamine gene expression during cellular damage and repair in central catecholamine neurons undergoing degeneration and regeneration. Project II, Olfactory afferent transneuronal regulation of catecholamine gene expression, will address the hypothesis that age-related alteration occurs in the steady- state expression of the TH gene and in the capacity of the gene to respond to perturbation. Project III, Signal transduction system and regulation of catecholamine gene expression, bridges the gap between the above in vivo studies that examine altered catecholamine enzyme gene expression and our on-going gene mapping studies to define the regulatory elements in these genes. The relationship between signal transduction pathways and the regulation of transcription of catecholamine enzymes will be investigated. Project IV, Molecular characterization of tryptophan hydroxylase (TPH), will utilize the molecular tools that have been developed during the current award period to study TPH gene regulation and further characterize TPH gene structure to identify elements responsible for transcriptional regulation. Experiments in this Program Project Grant focus on possible common cellular transduction pathways governing neurotransmitter gene expression under various physiological and pathophysiological conditions.